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Immunology (Subject) / Immunodeficiencies (Lesson)

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• Primary immunodeficiencies intrinsic defects in the immune system cells innate and heritable in newborn, baby and very young child
• Secondary immunodeficiencies acquired during life malnutrition trauma chemotherapy HIV radiotherapy immunosuppressive therapy
• Specific & non-specific specific: T&B-cells non-specific: complement & phagocytes
• Pyogenic infections encapsulated bacteria -antibody def. -complement def. -phagocytic cell dis.
• opportunistic infections ubiquitous MO normal people are resistant to cell-mediated immunity (t-cells)
• X-LA X- linked agammaglobulinemia - on X chromosome - no Ab - b-cell receptor dysfunctional
• Hyper IgM -no B-cell activation (cd40/cd40L) -no isotype switch/somatic hypermutation ( AID&UNG)
• SCID Severe combined immunodeficiency -no thymus development -defective γ-chain of IL-2 receptor -RAG1/2 def. (VDJ recombination)
• MHC II deficiency APC don't have MHCII def. of CD4+ cells -no CTL (no Th1) -only IgM (no Th2)
• Complement deficiency Autoimmune diseases: (C1/C4/C2) pyogenic bacteria: (block C3 convertase) Neisseria bacteria: (block C5-C9)
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• Phagocytic deficiencies Chronic granulomatous disease -defective NADPH oxidase -no superoxide anions -bacteria stay alive in phagocytes
• LAD 1 Leukocyte Adhesion deficiency 1 CR3 = no opsonization LFA1/selectins = no rolling
• LAD 2 Leukocyte Adhesion deficiency 2 -no fucosylation of glycoproteins - no Sialyl Lewis = no rolling
• HIV causes AIDS by depleting CD4+ T helper cells Disease: weakening of IS (Infections/cancer/opp. infections) needs anti-retroviral therapy vaccine may not be possible: too many mutants, HIV escapes IS

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